Lind, Evan F; Ahonen, Cory L; Wasiuk, Anna; Kosaka, Yoko; Becher, Burkhard; Bennett, Kathy A; Noelle, Randolph J (2008). Dendritic cells require the NF-kappaB2 pathway for cross-presentation of soluble antigens. Journal of Immunology, 181(1):354-363.
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NF-kappaB-inducing kinase (NIK) is responsible for activation of the non-canonical p100 processing pathway of NF-kappaB activation. This kinase has been shown to be critical for activation of this pathway after signaling through several TNF family members including CD40. The functional importance of this pathway in CD40 and TLR-induced dendritic cell (DC) differentiation was studied in vivo in the alymphoplasia (Aly) mouse. The Aly mouse expresses a mutant NIK molecule that prohibits the induction of the non-canonical pathway. We show that while MHC class II presentation and in vivo migration of Aly DCs is intact, these cells are unable to cross-prime CD8+ T cells to exogenous Ag. Gene expression array analysis of DCs matured in vivo indicates multiple defects in Ag processing pathways after maturation and provide a global view of the genes that are regulated by the NF-kappaB2 pathway in DCs. These experiments indicate a possible role for NIK in mediating cross-priming of soluble Ag. In addition, our findings explain the profound immune unresponsiveness of the Aly mouse.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > University Hospital Zurich > Institute of Experimental Immunology|
|DDC:||570 Life sciences; biology
610 Medicine & health
|Deposited On:||20 Jun 2012 07:22|
|Last Modified:||27 Apr 2014 06:59|
|Publisher:||American Association of Immunologists|
|Free access at:||PubMed ID. An embargo period may apply.|
|Citations:||Web of Science®. Times Cited: 20|
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